Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.
Journal
Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624
Informations de publication
Date de publication:
24 Dec 2021
24 Dec 2021
Historique:
entrez:
21
12
2021
pubmed:
22
12
2021
medline:
8
3
2022
Statut:
ppublish
Résumé
While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1β production, both at the transcriptional level and processing of pro–IL-1β. Consequently, atherosclerosis-prone mice lacking macrophage-specific
Identifiants
pubmed: 34932384
doi: 10.1126/sciimmunol.abf2489
pmc: PMC8902698
mid: NIHMS1767973
doi:
Substances chimiques
C5ar1 protein, mouse
0
IL1B protein, mouse
0
Interleukin-1beta
0
Receptor, Anaphylatoxin C5a
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabf2489Subventions
Organisme : NHLBI NIH HHS
ID : K22 HL125593
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R35 GM138283
Pays : United States
Organisme : NIAID NIH HHS
ID : K99 AI141622
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
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